Recurrent HSV-1 corneal disease is a significant problem that can lead to corneal scarring, which in turn can lead to decreased vision or blindness. Human and rabbit studies have revealed that viral shedding occurs extensively during active disease and that significant viral shedding occurs in the absence of corneal disease. The polymerase chain reaction (PCR) is a useful method for detecting HSV DNA. However, little has been done on the detection of HSV-1 DNA in the tears of latently infected mice. The study of mice is important because the mouse is a model relevant to the human condition and the genetic properties of the mouse can be varied to identify essential host components of HSV latency and reactivation. The aims of this proposal are 1) to document the detection of asymptomatic spontaneous shedding and symptomatic spontaneous reactivation of HSV-1 in mice and 2) to identify specific mouse (host) transcription factors that are important for HSV-1 spontaneous and induced reactivation in mice. These aims will be studied by obtaining tears from virus-infected wild type mice and mice with deletions in specific transcription factors. PCR will be used to detect and quantitate HSV-1 DNA. Fluorescence microscopy will be used to identify mouse ocular and nerve cells infected by a virus containing the enhanced green fluorescent protein (EGFP) gene. These aims will contribute to understanding the course of ocular HSV-1 latency and reactivation for wild type mice and mice deficient in transcription genes that are suspected to be involved in HSV-1 latency and reactivation.